Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
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DOI：
10.1021/jo960057x
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发表时间：
1996-05-31
影响因子：
3.6
通讯作者：
Shah, RD
中科院分区：
文献类型：
--
作者：
AbdelMagid, AF;Carson, KG;Shah, RD
三乙酰氧基硼氢化钠是醛酮还原胺化反应的常用还原剂。已经开发了用于各种底物的使用这种温和和选择性试剂的程序。反应的范围包括脂肪族无环和环状酮、脂肪族和芳香族醛、以及伯胺和仲胺，包括各种弱碱性和非碱性胺。限制包括与芳族和不饱和酮以及一些空间位阻酮和胺的反应。1，2-二氯乙烷（DCE）是优选的反应溶剂，但反应也可以在四氢呋喃（THF）中进行，偶尔在乙腈中进行。乙酸可用作酮反应的催化剂，但通常不需要用于醛反应。该过程在酸敏感官能团如缩醛和缩酮的存在下有效地进行;它也可以在可还原官能团如C-C多重键和氰基和硝基的存在下进行。反应通常在DCE中比在THF中更快，并且在两种溶剂中，在AcOH存在下反应更快。与NaBH_3CN/MeOH、硼烷-吡啶和催化氢化等还原胺化方法相比，NaBH（OAc）（3）的产率更高，副产物更少。在一些醛与伯胺的还原胺化反应中，其中二烷基化是一个问题，我们采用了一个分步程序，涉及在MeOH中形成亚胺，然后用NaBH 4还原。
Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH3CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH4.